SNA-modified antisense oligonucleotides: A new pathway for renal targeting?
Bernhard Dumoulin1,2,3,4, Ken Yamada5, Katalin Susztak1,2,3,4
1Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.
Molecular Therapy. Nucleic Acids
|March 4, 2025
Summary
New serinol nucleic acid (SNA)-modified antisense oligonucleotides (ASOs) show effective gene silencing in mouse kidneys with improved safety. These SNA-ASOs offer a promising approach for treating kidney diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Antisense oligonucleotides (ASOs) are therapeutic agents that suppress gene expression.
- Clinical use of ASOs is hindered by delivery issues and toxicity, especially with repeated or high doses.
- Targeting kidney diseases requires effective and safe therapeutic strategies.
Discussion:
- Tsuboi et al. developed serinol nucleic acid (SNA)-modified gapmer ASOs targeting sodium-glucose cotransporter 2 (SGLT2) in mouse kidneys.
- SNA-modified ASOs demonstrated dose-dependent efficacy and prolonged gene knockdown.
- These novel ASOs exhibited a better safety profile in kidney and liver tissues compared to 2'-MOE-modified ASOs.
Key Insights:
- SNA modification enhances the therapeutic potential of ASOs.
- Improved tolerability suggests reduced toxicity for ASO therapies.
- SGLT2 inhibition is a viable target for renal disease treatment using ASOs.
Outlook:
- SNA-modified ASOs represent a potential next-generation platform for treating renal diseases.
- Further research is needed to address high-dose toxicity concerns.
- This approach may enable more potent and tolerable ASO-based therapies.
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